The major goals of this project are to characterize the host's immune response to helminth infections and to relate these findings to the pathogenesis of clinical disease. Field studies of bancroftian filariasis suggest that initial exposure to these parasites elicits vigorous cellular immune responses but with continued reexposure, infected individuals cannot manifest significant cellular reactivity to filaria products. This defect in responsiveness is filaria-specific and limited to cellular immunity. Similar findings come from studies of human schistosomiasis mansoni. Patients evaluated within three months of initial infection demonstrated marked cellular reactivity to schistosome antigens, whereas lymphocytes from those with chronic infection were unable to respond to schistosome products. Studies of the cellular responses to helminth infections by lymphocytes and by eosinophil leukocytes as well as the mechanisms underlying the diminished reactivity to parasite antigens found in schistosomiasis and filariasis will continue both in experimental animals and in man.